Embryo Project Encyclopedia

Mechanism of Notch Signaling: The image depicts a type of cell signaling, in which two animal cells interact and transmit a molecular signal from one to the other. The process results in the production of proteins, which influence the cells as they differentiate, move, and contribute to embryological development. In the membrane of the signaling cell, there is a ligand (represented by a green oval). The ligand functions to activate a change in a receptor molecule. In the receiving cell, there are receptors; in this case, Notch proteins (represented by orange forks). The Notch proteins are embedded in the receiving cell membrane, and they have at least two parts: an intracellular domain (inside the cell) and the receptor (outside the cell). Once the ligand and receptor bind to each other, a protease (represented by the dark red triangle) can sever the intracellular domain from the rest of the Notch receptor. Inside the nucleus of the receiving cell (represented by the gray area) are the cellês DNA (represented by the multi-colored helices) and its transcription factors (blue rectangles). Transcription factors are proteins that bind to DNA to regulate transcription, the first step in gene expression, which eventually yields proteins or other products. Initially, repressor proteins (represented by a red irregular hexagon) prevent transcription factors from allowing transcription. When the severed Notch receptor intracellular domain reaches the nucleus, it displaces the repressor. The transcription factor can then signal for transcription to occur. 1) There is a Notch receptor protein in the membrane of a receiving cell, and a ligand for this receptor (for example, Delta) in the membrane of the signaling cell. When the ligand binds to the receptor, the intracellular domain of the receptor changes shape. 2) Inside the receiving cell, there are proteases. Once the intracellular domain of the receptor changes shape, the protease can bind to it and shear the intracellular domain away from the rest of the receptor molecule. 3) The severed intracellular domain is shuttled to the receiving cell nucleus. Here, the intracellular domain displaces a repressor protein. This allows a transcription factor to initiate DNA transcription. During transcription, DNA is used as a template to create RNA. Following transcription, the process of translation occurs, which uses RNA as a template to create proteins. These proteins influence the behavior, fate, and differentiation of cells, which contribute to normal embryonic development

'On the Permanent Life of Tissues outside of the Organism' reports Alexis Carrel's 1912 experiments on the maintenance of tissue in culture media. At the time, Carrel was a French surgeon and biologist working at the Rockefeller Institute in New York City. In his paper, Carrel reported that he had successfully maintained tissue cultures, which derived from connective tissues of developing chicks and other tissue sources, by serially culturing them. Among all the tissue cultures Carrel reported, one was maintained for more than two months, whereas previous efforts had only been able to keep tissues in vitro for three to fifteen days. Carrel’s experiments contributed to the development of long-term tissue culture techniques, which were useful in the study of embryology and eventually became instrumental in stem cell research. Despite later evidence to the contrary, Carrel believed that as long as the tissue culture method was accurately applied, tissues kept outside of the organisms should be able to divide indefinitely and have permanent life.

The p53 protein acts as a pivotal suppressor of inappropriate cell proliferation. By initiating suppressive effects through induction of apoptosis, cell senescence, or transient cell-cycle arrest, p53 plays an important role in cancer suppression, developmental regulation, and aging. Its discovery in 1979 was a product of research into viral etiology and the immunology of cancer. The p53 protein was first identified in a study of the role of viruses in cancer through its ability to form a complex with viral tumor antigens. In the same year, an immunological study of cancer also found p53 due to its immunoreactivity with tumor antisera. Although a series of studies found p53 through various routes, and various researchers called it different names, it was eventually confirmed that they had all encountered the same protein, p53.

Christiane Nusslein-Volhard studied how genes control embryonic development in flies and in fish in Europe during the twentieth and twenty-first centuries. In the 1970s, Nusslein-Volhard focused her career on studying the genetic control of development in the fruit fly Drosophila melanogaster. In 1988, Nusslein-Volhard identified the first described morphogen, a protein coded by the gene bicoid in flies. In 1995, along with Eric F. Wieschaus and Edward B. Lewis, she received the Nobel Prize in Physiology or Medicine for the discovery of genes that establish the body plan and segmentation in Drosophila. Nusslein-Volhard also investigated the genetic control of embryonic development to zebrafish, further generalizing her findings and helping establishing zebrafish as a model organism for studies of vertebrate development.

In a series of experiments between 1960 and 1965, Robert Geoffrey Edwards discovered how to make mammalian egg cells, or oocytes, mature outside of a female's body. Edwards, working at several research institutions in the UK during this period, studied in vitro fertilization (IVF) methods. He measured the conditions and timings for in vitro (out of the body) maturation of oocytes from diverse mammals including mice, rats, hamsters, pigs, cows, sheep, and rhesus monkeys, as well as humans. By 1965, he manipulated the maturation of mammalian oocytes in vitro, and discovered that the maturation process took about the same amount of time as maturation in the body, called in vivo. The timing of human oocyte maturation in vivo, extrapolated from Edwards's in vitro study, helped researchers calculate the timing for surgical removal of human eggs for IVF.

In the early 1960s, John W. Saunders Jr., Mary T. Gasseling, and Lilyan C. Saunders in the US investigated how cells die in the developing limbs of chick embryos. They studied when and where in developing limbs many cells die, and they studied the functions of cell death in wing development. At a time when only a few developmental biologists studied cell death, or apoptosis, Saunders and his colleagues showed that researchers could use embryological experiments to uncover the causal mechanisms of apotosis. The researchers published many of their results in the 1962 paper 'Cellular death in morphogenesis of the avian wing.'

In 1969, Roy J. Britten and Eric H. Davidson published Gene Regulation for Higher Cells: A Theory, in Science. A Theory proposes a minimal model of gene regulation, in which various types of genes interact to control the differentiation of cells through differential gene expression. Britten worked at the Carnegie Institute of Washington in Washington, D.C., while Davidson worked at the California Institute of Technology in Pasadena, California. Their paper was an early theoretical and mechanistic description of gene regulation in higher organisms.

To Lynn M. Morgan, the Mary E. Woolley Professor of Anthropology at Mt. Holyoke College, nothing says life more than a dead embryo. In her easily readable book, Icons of Life: A Cultural History of Human Embryos, Morgan brings together cultural phenomena, ethics, and embryology to show that even dead embryos and fetuses have their own stories to tell. As an anthropologist, Morgan is interested in many things, including the science of embryology and its history. But she also wants to know how culture influences our views on embryos and the material practices that accompany their study. Her intent is to establish a relationship between specimens collected in the remote past and the contemporary cultural politics of abortion (p. xiii). The eight chapters in Icons of Life do not provide an exhaustive historical look at early American embryology, but they do weave together the Carnegie Institute of Washington Embryology Department (CIWED), its major human embryo collector Franklin Paine Mall, and how early twentieth-century science worked. Morgan ably describes the CIWEDÕs early foray into embryo collecting, but she wants to do more than just describe how embryos made their way to the laboratory. She wants us to ask why it was even possible for such a thing to happen without so much as a fuss being made from the public. This involves looking at culture.

German embryologist Viktor Hamburger came to the US in 1932 with a fellowship provided by the Rockefeller Foundation. Hamburger started his research in Frank Rattray Lillie's laboratory at the University of Chicago. His two-year work on the development of the central nervous system (CNS) in chick embryos was crystallized in his 1934 paper, "The Effects of Wing Bud Extirpation on the Development of the Central Nervous System in Chick Embryos," published in The Journal of Experimental Zoology. Hamburger was able to use the microsurgical techniques that he had learned from Hans Spemann to show how wing buds influence the development of the CNS in chick embryos. This paper is one of several among Hamburger's important studies on chick embryos and represents the empirical and theoretical cornerstone for his further research on central-peripheral relations in the development of the nervous system.

An important question throughout the history of embryology is whether the formation of a biological structure is predetermined or shaped by its environment. If both intrinsic and environmental controls occur, how exactly do the two processes coordinate in crafting specific forms and functions? When Viktor Hamburger started his PhD study in embryology in the 1920s, few neuroembryologists were investigating how the central neurons innervate peripheral organs. As Hamburger began his research, he had no clue that central-peripheral relations in the development of the central nervous system (CNS) would become one of his major interests for the next seventy-five years. In fact, this research trajectory would lead him to discover programmed cell death as a pivotal mechanism mediating central-peripheral relations, as well as to Nobel-Prize-winning work on nerve growth factors (NGF).